The investigative program concerns the relationship of bile acid synthesis, metabolism and excretion to bile flow. Basic mechanisms obtained from physiological studies in vivo and biochemical studies in vitro are applied to the problem of cholestatic liver disease. These studies include (1) the further development of methods of bile acid analysis to permit the routine detection of anicteric neonatal cholestasis (2) detailed analysis of bile acid composition of cholestatic urine and in vivo studies of the route of excretion of sulfated bile acids and their role as competitive inhibitors of nonsulfated bile acid excretion (3) an in vitro enzyme system for kinetic analysis of metabolism of cholesterol to bile acid via 7 alpha and 26-hydroxycholesterol with sulfotransferase activity for the purpose of studying factors regulating pathways of synthesis (4) in vivo studies of the effect of drugs metabolized as ester sulfates on the esterification of bile acids (5) validation of isotope dilution techniques (Linstedt) for estimation of bile acid synthesis and turnover during experimental cholestasis in animals and its application to bile acid balance studies in cholestatic syndromes including therapeutic response to medications.